OBJECTIVES Active-comparator, non-inferiority study designs are used in uncomplicated urinary tract infection (uUTI) to establish the efficacy of a new antibacterial, given the availability of effective antibiotics. We estimate the treatment effect of a planned antimicrobial comparator (nitrofurantoin), from historical trial data, to properly design an upcoming non-inferiority study in uUTI. METHODS A systematic literature review and meta-analysis were conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines which incorporate recommendations for standardized data quality assessment, reporting of results, risk of bias assessment and sensitivity analyses. To account for inter-study variability, a weighted non-iterative, random effects model was fit, using R software to obtain estimates of the microbiological response rate and corresponding 95% CI for nitrofurantoin and placebo treatment. Inter-study heterogeneity was assessed, with Cochran's chi-square test for inter-study heterogeneity; I2 statistic and P values were computed and included in the forest plot of the meta-analysis. RESULTS Twelve unique studies met the final eligibility criteria for meta-analysis inclusion; 3 trials assessed placebo efficacy, 8 trials assessed nitrofurantoin efficacy, and one study assessed both nitrofurantoin and placebo efficacy in uUTI. The overall microbiological response (95% confidence interval) was 0.766 (0.665, 0.867) for nitrofurantoin and 0.342 (0.288, 0.397) for placebo. CONCLUSION The corresponding treatment effect estimate for nitrofurantoin was 26.8%, which supports a conservative non-inferiority margin of 12.5% and is consistent with the recently published draft FDA guidance. The findings from this systematic review and meta-analysis inform future antibacterial trials by providing non-inferiority margin justification. BACKGROUND Fluconazole resistance in Candida tropicalis healthcare associated infections is on rise. We investigated the role of efflux pump and mutations in ERG11p conferring fluconazole resistance in C. tropicalis. MATERIALS AND METHODS A total of seventeen C. tropicalis clinical isolates, including fluconazole resistant and fluconazole susceptible/susceptible dose dependent were collected from a tertiary care center in North India region between 2015 and 2018. Antifungal susceptibility, reversal of fluconazole resistance by tacrolimus, ERG11 amplification and sequencing and quantitative PCR for expression analysis of ERG11, MDR1, and CDR1 were performed. RESULTS AND DISCUSSION Synergism between fluconazole and tacrolimus was observed in all resistant C. tropicalis isolates. Overexpression of all the three genes, MDR1, ERG11 and CDR1 was observed in resistant isolates (p value?=?0.05). Among resistant isolates, mutation leading to amino acid substitution was seen in two, Ct10 (Glysine464Serine) and Ct16 (Tyrosine132Phenylalanine; Serine154Phenylalanine). CONCLUSION Overexpression in efflux pump transporter genes together with mutations in ERG11 pave the way to fluconazole resistance among C. tropicalis. To the best of our knowledge this is the first study on C. tropicalis fluconazole resistance mechanism from North India region. OBJECTIVES The aim of this study was to evaluate antibiotic susceptibility patterns in commercially available dietary and probiotic supplements. METHODS Probiotic strains were isolated from the dietary supplements (designated as sample B, D and V) and multidrug resistance profiles were tested using the Kirby-Bauer test. Minimum inhibitory concentrations and double disk synergy tests were performed to detect the mechanism of action of the resistance and presence of extended spectrum of β- lactamase activity (ESBL) was confirmed. RESULTS The isolates S. faecalis and B. mesentericus (both from sample B) were found to be resistant to penicillin G, L. acidophilus (sample D) was resistant to ampicillin, and all of the isolates from samples B, D, and V were resistant to ceftazidime. The isolates L. sporogenes, S. faecalis, B. mesentericus from sample B, L. rhamnosus, S. boulardi from sample D and L. https://www.selleckchem.com/ sporogenes (sample V), were resistant to erythromycin. CONCLUSIONS The findings showed the presence of antibiotic resistance in probiotic bacteria isolated from commercially available dietary supplements. As multidrug resistance is a serious emerging issue and the risk of drug resistant gene transfer to commensals or pathogens of the gut is inevitable, the safety of probiotics has become a major criterion of interest. The findings of this study would serve as a platform for further screening and characterization of the determinants of antibiotic resistance and the genetic mechanisms of resistance. OBJECTIVES As a common nosocomial infection bacterium, A. baumannii's drug resistance rate continues to rise. In this study, the objective was to explore the possible reasons for the increased drug resistance of A. baumannii after tigecycline treatment. METHODS Based on the drug resistance analysis of 183 clinical isolates of A. baumannii, a pair of strains (AB711 and AB721) which changed their resistance after treatment was selected. Tigecycline was used to induce the drug resistance of strain AB711 in vitro. The differential expressed genes from A. baumannii strains were analyzed using whole gene sequencing (WGS ) and RNA sequencing (RNA-seq) combined with online MLST, SNP tools and bioinformatics software, and verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS AB721 became more resistant to tetracyclines than AB711 at the initial detection. However, after a period of time, the resistance of AB711 and AB721 became consistent. This phenomenon can also be repeated using AB711 in vitro. After induction, the AB711 with increased MIC value of tigecycline was named AB712. The results of WGS, MLST and SNP based Phylogenetic tree indicated that AB711, AB712, AB721 were co-origin and belong to ST2 (Pasteur) / ST1791 (Oxford). Comparative transcriptome indicated that the Differential expression of some genes can play an important role in the resistance enhancement process of AB711. For example, compared with AB711, genes related to benzene-containing compound metabolic process, translation, ribosomal structure and biogenesis and so on were upregulated significantly in AB712. In addition, efflux pumps such as RND transporter permease subunit, EmrAB, MacB, and Tet resistance operon were also upregulated. CONCLUSION Tigcycline induced changes in the expression of some related genes in A. baumannii, which may be the main reason for its increased drug resistance.